Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats

Kobelt, Peter; Helmling, Steffen; Stengel, Andreas; Wlotzka, Britta; Andresen, Viola; Klapp, B. F.; Wiedenmann, Bertram; Klussmann, Sven; Mönnikes, Hubert

doi:10.1136/gut.2004.061010

Cited by 64 publications

(46 citation statements)

References 34 publications

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“…Supportively, previous studies show that NOX‐B11‐2 decreased food intake in rodents via ghrelin‐dependent mechanisms (Kobelt et al., 2006; Shearman et al., 2006). In both rodents and humans, the plasma levels of ghrelin increase preprandially and thereby induce food intake (for review, see Egecioglu et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…1). In rats, a dose of 20 mg/kg (IP) was administrated since previous studies show that a similar dose reduces ghrelin‐induced food intake (Kobelt et al., 2006; Shearman et al., 2006). NOX‐B11‐2 was always administered IP 60 minutes prior to drug challenge as this is the time frame required for NOX‐B11‐2 to bind to circulating ghrelin and prevents its access to the brain (Shearman et al., 2006).…”

Section: Methodsmentioning

confidence: 99%

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Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Jerlhag

Ivanoff

Vater

et al. 2014

Alcoholism Clin & Exp Res

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BackgroundDevelopment of alcohol dependence, a chronic and relapsing disease, largely depends on the effects of alcohol on the brain reward systems. By elucidating the mechanisms involved in alcohol use disorder, novel treatment strategies may be developed. Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor 1A, acts as an important regulator of energy balance. Recently ghrelin and its receptor were shown to mediate alcohol reward and to control alcohol consumption in rodents. However, the role of central versus peripheral ghrelin for alcohol reward needs to be elucidated.MethodsGiven that ghrelin mainly is produced by peripheral organs, the present study was designed to investigate the role of circulating endogenous ghelin for alcohol reward and for alcohol intake in rodents.ResultsWe showed that the Spiegelmer NOX‐B11‐2, which binds and neutralizes acylated ghrelin in the periphery with high affinity and thus prevents its brain access, does not attenuate the alcohol‐induced locomotor activity, accumbal dopamine release and expression of conditioned place preference in mice. Moreover, NOX‐B11‐2 does not affect alcohol intake using the intermittent access 20% alcohol 2‐bottle‐choice drinking paradigm in rats, suggesting that circulating ghrelin does not regulate alcohol intake or the rewarding properties of alcohol. In the present study, we showed however, that NOX‐B11‐2 reduced food intake in rats supporting a role for circulating ghrelin as physiological regulators of food intake. Moreover, NOX‐B11‐2 did not affect the blood alcohol concentration in mice.ConclusionsCollectively, the past and present studies suggest that central, rather than peripheral, ghrelin signaling may be a potential target for pharmacological treatment of alcohol dependence.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Jerlhag

Ivanoff

Vater

et al. 2014

Alcoholism Clin & Exp Res

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“…It blocks the biological effect by preventing ghrelin's activation of the endogenous receptor (Helmling et al 2004). The effects of ghrelin neutralization with NOX-B11(2) and related compounds on growth M a n u s c r i p t 6 hormone secretion, food intake and body weight gain in diet-induced obese mice were previously demonstrated (Helmling et al 2004;Kobelt et al 2006;Shearman et al 2006).…”

Section: Page 5 Of 37mentioning

confidence: 98%

Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism

Sangiao‐Alvarellos

Helmling

Vázquez

et al. 2011

Molecular and Cellular Endocrinology

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Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism.. Molecular and Cellular Endocrinology, Elsevier, 2011, 335 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 of 37A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 2 ABSTRACT Ghrelin, a hormone whose levels increase during food deprivation, plays a pivotal role in the regulation of food intake, energy metabolism and storage, as well as in insulin sensitivity. Here, we investigated the effects of acyl-ghrelin neutralization with the acyl-ghrelin-binding compound NOX-B11(2) during the fasting-refeeding cycle. Our data demonstrate that ghrelin neutralization with NOX-B11(2) impairs recuperation of lost body weight after food deprivation. Analysis of enzymes involved in glucose and lipid metabolism in liver of fed, fasted and refed rats revealed that neutralization of acyl-ghrelin resulted in minor decreases in the enzymes of glycolytic and lipogenic pathways during fasting. However, during refeeding these enzymes as well as glycogen levels recovered more slowly when acyl-ghrelin was blocked. The high levels of ghrelin in response to food deprivation may contribute to an adequate decrease in hepatic glycolytic and lipogenic enzymes and aid in the recovery of body weight and energetic reserves once food becomes available after the fasting period.

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“…Intravenous administration to rats of NOX-B11, a ghrelin spiegelmer, sup-pressed ghrelin-induced neuronal activity and ghrelin-induced food intake [126]. Another novel approach to reduce the effect of circulating ghrelin is the use of anti-ghrelin vaccines.…”

Section: Ghrelinmentioning

confidence: 99%

Peptides and Their Potential Role in the Treatment of Diabetes and Obesity

Greenwood

Bloom²,

Murphy

2011

Rev Diabet Stud

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■ AbstractIt is estimated that 347 million people worldwide have diabetes and that over 1.5 billion adults worldwide are overweight. Predictions suggest these rates are increasing. Diabetes is a common complication in overweight and obese subjects, and in 2004, an estimated 3.4 million people died from consequences of high blood sugar. Thus, there is great interest in revealing the physiological systems that regulate body weight and blood sugar. Several peptidergic systems within the central nervous system and the periphery regulate energy homeostasis. A number of these systems have been investigated as potential treatments for obesity and the metabolic syndrome. However, manipulation of peptidergic systems poses many problems. This review discusses the peptidergic systems currently attracting research interest for their clinical potential to treat obesity. We consider first neuropeptides in the brain, including the orexigenic neuropeptide Y and melanin-concentrating hormone, and anorectic factors such as the melanocortins, ciliary neurotrophic factor, and neuromedin U. We subsequently discuss the utility of targeting peripheral gut peptides, including pancreatic polypeptide, peptide YY, amylin, and the gastric hormone ghrelin. Also, we analyze the evidence that these factors or drugs based on them may be therapeutically useful, while considering the disadvantages of using such peptides in a clinical context.

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Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats

Cited by 64 publications

References 34 publications

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Peripherally Circulating Ghrelin Does Not Mediate Alcohol‐Induced Reward and Alcohol Intake in Rodents

Ghrelin neutralization during fasting-refeeding cycle impairs the recuperation of body weight and alters hepatic energy metabolism

Peptides and Their Potential Role in the Treatment of Diabetes and Obesity

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